Bristol Myers Squibb Announces Final Results from CheckMate-227 Part 1: Opdivo Plus Low-Dose Yervoy Demonstrates Significant Overall Survival Benefit Over Chemotherapy in First-Line Advanced NSCLC

Recently, Bristol-Myers Squibb announced the final results from Part 1 of the Phase III CheckMate 227 clinical trial, which evaluated the efficacy of Opdivo combined with low-dose ipilimumab as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The combination of Opdivo and low-dose ipilimumab met the study’s independent co-primary endpoint, namely overall survival (OS) in patients with PD-L1 expression ≥1%. The results demonstrated that, compared with chemotherapy, this combination therapy provided a significant overall survival benefit in patients with PD-L1 ≥1% [HR 0.79; 97.72% CI: 0.65 to 0.96]. Furthermore, exploratory analysis revealed that Opdivo combined with low-dose ipilimumab improved overall survival in patients with PD-L1 <1% [HR 0.62; 95% CI: 0.48 to 0.78]. The 2-year survival rate with the combination regimen was 40% in both the PD-L1 ≥1% and PD-L1 <1% populations, whereas the corresponding 2-year survival rates in the chemotherapy group were 33% and 23%, respectively.

This is the first and only clinical study demonstrating that dual immunotherapy combination treatment, compared with chemotherapy, provides significant survival benefits for patients as first-line therapy for non-small cell lung cancer (NSCLC). The study results will be presented at the Presidential Symposium of the 2019 European Society for Medical Oncology (ESMO) Congress held in Barcelona, Spain.

The safety profile of Opdivo in combination with low-dose ipilimumab was consistent with previously reported findings in non-small cell lung cancer (NSCLC) studies, with no new safety signals observed.

At a minimum follow-up of 29.3 months, the duration of response (DoR) for patients treated with Opdivo combined with low-dose ipilimumab was nearly four times that of patients receiving chemotherapy, regardless of PD-L1 expression levels. In patients with PD-L1 ≥1%, the objective response rate (ORR) for those treated with Opdivo plus low-dose ipilimumab was 35.9% (95% CI, 31.1 to 40.8), with a complete response rate of 5.8%, compared to an ORR of 30.0% (95% CI, 25.5 to 34.7) and a complete response rate of 1.8% in the chemotherapy group. The median DoR in the combination therapy group was 23.2 months, whereas it was only 6.2 months in the chemotherapy group. In patients with PD-L1 <1%, the ORR for those treated with Opdivo plus low-dose ipilimumab was 27.3% (95% CI, 30.7 to 45.4), with a complete response rate of 2.1%, compared to an ORR of 23.1% (95% CI, 17.3 to 29.8) and a complete response rate of 1.1% in the chemotherapy group. The median duration of response (mDoR) in the combination therapy group was 18 months, compared to only 4.8 months in the chemotherapy group.

“These positive results validate the immunological rationale for dual immune checkpoint PD-1 and CTLA-4 blockade in the treatment of lung cancer,” said a CheckMate 227 investigator from the Lung Clinic Grosshansdorf, GermanyMedicineMartin Reck, Ph.D., stated, “The study results demonstrate that dual immune checkpoint inhibitor combination therapy for first-line non-small cell lung cancer can yield deep and durable responses, as well as clear survival benefits, offering patients a ‘chemotherapy-free’ treatment option.”

“The announcement of the CheckMate 227 Part 1 data establishes Opdivo in combination with Yervoy as the first and only dual-immunotherapy regimen to demonstrate superior overall survival compared to chemotherapy in the first-line treatment of non-small cell lung cancer,” said Fouad Namouni, M.D., Head of Oncology R&D at Bristol-Myers Squibb. “These findings, building upon long-term clinical data in first-line melanoma and renal cell carcinoma, confirm the benefits of Opdivo plus Yervoy over standard of care. We look forward to sharing these data with regulatory authorities and, through ongoing research, further expanding our understanding of the value this unique combination offers to patients with cancer.”

(Ipilimumab has not yet been marketed in mainland China)

Regarding the CheckMate 227 Study

CheckMate 227 is a multicenter, open-label, Phase III clinical study evaluating Opdivo®-based regimens versus platinum-doublet chemotherapy in patients with previously untreated advanced non-small cell lung cancer (NSCLC), including both squamous and non-squamous histologies. The study comprises the following parts:

Part 1:

- Part 1a: To evaluate the efficacy of Opdivo in combination with low-dose ipilimumab and Opdivo monotherapy compared with chemotherapy in patients with PD-L1 expression

-Part 1b: In patients not expressing PD-L1, evaluate the efficacy of Opdivo combined with low-dose ipilimumab and Opdivo combined with chemotherapy compared to chemotherapy alone.

Part 2: Efficacy Evaluation of Opdivo Combined with Chemotherapy versus Chemotherapy Alone, Irrespective of PD-L1 Expression Status

Part 1 of the study had two primary endpoints in the evaluation of Opdivo combined with Yervoy (versus chemotherapy): one was overall survival (OS) in patients with PD-L1–expressing tumors (assessed in Part 1a), and the other was progression-free survival (PFS) in patients with high tumor mutational burden (TMB ≥ 10 mutations/Mb, regardless of PD-L1 expression status) (assessed in Parts 1a and 1b). In Part 1, the trial met the co-primary endpoint of PFS for patients with high tumor mutational burden (TMB ≥ 10 mutations/Mb) when Opdivo was combined with Yervoy compared with chemotherapy, irrespective of PD-L1 expression status. Furthermore, compared with chemotherapy, first-line treatment with Opdivo plus low-dose Yervoy in patients with non-small cell lung cancer (NSCLC) and PD-L1 ≥ 1% resulted in greater OS benefit. In Part 2, among patients with non-squamous NSCLC, the study of Opdivo combined with chemotherapy did not meet the primary endpoint of OS compared with chemotherapy.